Role of the protein kinase C λ/ι isoform in nuclear factor-κB activation by interleukin-1β or tumor necrosis factor-α: cell type specificities

Giuseppina Bonizzi, Jacques Piette, Sonia Schoonbroodt, Marie Paule Merville, Vincent Bours

Research output: Contribution to journalArticle

Abstract

It has previously been reported that distinct signaling pathways can lead to nuclear factor (NF)-κB activation following stimulation of different cell types with inflammatory cytokines. As the role of atypical protein kinase C (PKC) isoforms in NF-κB activation remains a matter of controversy, we investigated whether this role might be cell type-dependent. Immunoblots detected atypical PKC expression in all the analyzed cell lines. The PKC inhibitor calphostin C inhibited NF-κB activation by tumor necrosis factor (TNF)-α or interleukin (IL)-1β in Jurkat or NIH3T3 cells but not in MCF7 A/Z cells. Cell transfections with a PKC λ/ι dominant negative mutant abolished TNF-α-induced NF-κB-dependent transcription in NIH3T3 and Jurkat cells but not in MCF7 A/Z cells. Similarly, the same mutant blocked NF-κB-dependent transactivation after IL-1β stimulation of NIH3T3 cells, but was ineffective after IL-1β treatment of MCF7 A/Z cells. In MCF7 A/Z cells, however, the PKC λ/ι dominant negative mutant could abolish transactivation of an AP-1-dependent reporter plasmid after stimulation with TNF-α but not with IL-1β. These data thus confirm that transduction pathways for NF-κB activation after cell stimulation with TNF-α or IL-1β are cell-type specific and that atypical PKC isoforms participate in this pathway in NIH3T3 and Jurkat cells. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalBiochemical Pharmacology
Volume57
Issue number6
DOIs
Publication statusPublished - Mar 15 1999

Keywords

  • IL-1β
  • NF-κB
  • Protein kinase C
  • Signal transduction
  • TNF-α

ASJC Scopus subject areas

  • Pharmacology

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